title: Mmp17b is essential for proper neural crest cell migration in vivo.
abstract: The extracellular matrix plays a critical role in neural crest (NC) cell migration. In this study, we characterize the contribution of the novel GPI-linked matrix metalloproteinase (MMP) zebrafish mmp17b. Mmp17b is expressed post-gastrulation in the developing NC. Morpholino inactivation of mmp17b function, or chemical inhibition of MMP activity results in aberrant NC cell migration with minimal change in NC proliferation or apoptosis. Intriguingly, a GPI anchored protein with metalloproteinase inhibitor properties, Reversion-inducing-Cysteine-rich protein with Kazal motifs (RECK), which has previously been implicated in NC development, is expressed in close apposition to NC cells expressing mmp17b, raising the possibility that these two gene products interact. Consistent with this possibility, embryos silenced for mmp17b show defective development of the dorsal root ganglia (DRG), a crest-derived structure affected in RECK mutant fish sensory deprived (sdp). Taken together, this study has identified the first pair of MMP, and their putative MMP inhibitor RECK that functions together in NC cell migration.
authors.affiliation: Department of Pediatrics, Developmental Vascular Biology Program, Children's Research Institute (CRI), Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Noah R
authors.initials: NR
authors.lastname: Leigh
authors.forename: Marcus-Oliver
authors.initials: MO
authors.lastname: Schupp
authors.forename: Keguo
authors.initials: K
authors.lastname: Li
authors.forename: Vakeel
authors.initials: V
authors.lastname: Padmanabhan
authors.forename: Adam
authors.initials: A
authors.lastname: Gastonguay
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Chang Z
authors.initials: CZ
authors.lastname: Chun
authors.forename: George A
authors.initials: GA
authors.lastname: Wilkinson
authors.forename: Ramani
authors.initials: R
authors.lastname: Ramchandran
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics; D004789:Enzyme Activation; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D053515:Matrix Metalloproteinase 17 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D016415:Sequence Alignment; D015027:Zebrafish
chemical_list: D058851:GPI-Linked Proteins; D053515:Matrix Metalloproteinase 17